arterial therapies. This study sought to assess the major complication rates associated with arterial and venous lytic therapies with the hypothesis that the complication rates may be higher with venous as compared to arterial treatments.Methods: This study is a single-center, retrospective review of arterial and venous lytic treatments that were performed between the dates of December 2010 and April 2015. Treatment areas included all arterial and venous beds; however, dialysis access and pulmonary embolism treatments were excluded from the analysis. Treatment protocols for lytic therapy were standardized, with modifications made according to attending discretion. During the pharmacomechanical thrombectomy portion, the appropriate AngioJet rheolytic catheter was used based on the target vessel diameter. A maximum of 10 mg of tPA was used at the index treatment. Lytic therapy was continued postoperatively at a rate of 1 mg/h. This was titrated postoperatively based on serial laboratory examinations of fibrinogen, CBC, PTT, and CPK (arterial cases). The tPA was titrated based on the fibrinogen level: fibrinogen 200-250 (tPA at 0.5 mg/h); fibrinogen <200 (tPA held); fibrinogen <100 or any sign of bleeding (tPA reversal). Access site and systemic complications were evaluated.Results: A total of 93 patients were included in the cohort (A-52 vs V-41). The gender breakdown (% women) did not differ significantly between the two cohorts (A-63% vs V-78%; P ¼ .17). The age did differ significantly between the two cohorts (A-68 years vs V-50 years; P < .01). There were 6 complications (11.5%) in the arterial lytic group, with one associated mortality, and 6 complications (14.6%) in the venous lytic group (P ¼ NS). There were no significant differences in the total number of complications, although the complication types trended towards an increase in systemic complications in the venous patients (P ¼ .2; Table ).Conclusions: This study suggests that the overall complication rates as related to venous lytic therapy are equivalent to those for arterial lytic therapy; however, the nature of the complications may differ, with a trend toward increased systemic complications in venous patients. This study provides for further impetus to evaluate venous lytic treatments as a separate entity from arterial lytic treatments, specifically with regards to indications for treatment, procedural technique and tPA dosing.

Biosensor measurement of transdermal alcohol oncentration in perspiration exhibits significant variance from subject to subject and device to device. Short duration data collected in a controlled clinical setting is used to calibrate a forward model for ethanol transport from the blood to the sensor. The calibrated model is then used to invert transdermal signals collected in the field (short or long duration) to obtain an estimate for breath measured blood alcohol concentration. A distributed parameter model for the forward transport of ethanol from the blood through the skin and its processing by the sensor is developed. Model calibration is formulated as a nonlinear least squares fit to data. The fit model is then used as part of a spline based scheme in the form of a regularized, non-negatively constrained linear deconvolution. Fully discrete, steepest descent based schemes for solving the resulting optimization problems are developed. The adjoint method is used to accurately and efficiently compute requisite gradients. Efficacy is demonstrated on subject field data.

The nitric oxide (NO) produced by inducible Nitric Oxide Synthase (iNOS) up-regulates the expression of heme oxygenase (HO), which in turn produces carbon monoxide (CO) that down-regulates iNOS activity by reducing its expression level or by inhibiting its activity by converting it to an inactive P420 form (iNOSP420). Accordingly, CO has been considered as a potentially important attenuator of inflammation. Despite its importance, the nature of the proximal heme ligand of the iNOSP420 species remains elusive. Here we show that the 221 cm−1 mode of the photoproduct of iNOSP420 does not exhibit any H2O-D2O solvent isotope shift such as that found in the iron-histidine stretching mode of myoglobin, indicating that the proximal ligand of iNOSP420 is not a histidine. The νFe-CO and νC-O data reveal that the proximal heme ligand of iNOSP420 is consistent with a protonated thiol, instead of a thiolate anion. Furthermore, the optical absorption properties of iNOSP420 are similar to those of a neutral thiol-heme model complex, but not myoglobin. Together the data support the scenario that iNOSP420 is inactivated by protonation of the native proximal thiolate ligand to a neutral thiol, instead of by ligand switching to a histidine, as prior studies have suggested.

Background: Trp-188 plays a role in regulating the activity of nitric-oxide synthase (NOS). Results: W188H mutation stabilizes a 420-nm intermediate by distorting the heme macrocycle. Conclusion: The 420-nm intermediate is a hydroxide-bound ferric heme species with a tetrahydrobiopterin radical center. Significance: The data provide the first evidence for a critical intermediate in NOS.

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